The purpose of this contract is to determine the in vitro affinity for and inhibitory activity of test compounds on the human dopamine, serotonin and norepinephrine transporters. The data generated by this contract will be utilized by the NIDA Medications Development Division Cocaine Treatment Discovery Program in the selection of compounds for in vivo preclinical evaluations. Cocaine and a number of other abused substances bind to each of the biogenic amine transporters, and block the uptake of the respective neurotransmitter. This effect is hypothesized to play a crucial role in cocaine's reinforcing effects and potential for addition, and represents a logical target for medication development efforts. Further, recent work on NIDA Contract N01DA38303 indicates that, using novel compounds, it is possible to separate the affinity of a drug for the cocaine binding site on the transporter from its potency at blocking neurotransmitter uptake. Thus, this contract will seek to identify drugs that have a high affinity for the cocaine binding site, and prevent the binding of cocaine, but have a relatively low potency at blocking neurotransmitter uptake.